Prior studies indicate that lateralization of function is altered in depressed patients. We propose to use a battery of behavioral measures of cognitive and affective lateralization, in conjunction with more direct event-related potential (ERP) and EEG measures of hemispheric asymmetry, to help clarify the nature of the lateralized hemispheric involvement in different diagnostic subtypes of affective disorder. All patients will be tested both before and after treatment with antidepressant medication so as to determine whether alterations of lateral asymmetry in depressed patients persist or disappear with remission of depression following treatment. The objective is to determine which behavioral, ERP and EEG measures of lateral asymmetry are dependent on pre- vs. post-treatment changes in clinical state and which are most stable trait variables. A further objective is to assess the value of individual difference measures of ear, visual field, ERP and EEG asymmetry in predicting therapeutic response to antidepressant medication. The clinical relevance of this objective lies in the need for more precise diagnostic aids that facilitate the selection of treatments tailored to different subtypes of affective disorder. We propose to test 30 bipolar depressed patients (half Bipolar I and half Bipolar II), 30 unipolar depressed patients and 30 normal controls. Patients will initially be tested after a minimum drug-free period of 10 days. They will then be retested following six weeks of treatment with an antidepressant, and bipolar patients will, in addition, be tested during a euphoric phase. Normal controls will also be retested at the same test-retest intervals as patients. Our specific aims are: (1) to simultaneously measure ear and ERP asymmetries of the patient groups and controls in parallel temporal and spatial tasks that tap primarily left versus right hemispheric function; (2) to measure visual field asymmetries in parallel verbal and spatial tasks so as to assess the modality specificity of findings; (3) to examine whether alterations of ear/visual field asymmetries in depressed patients extend to the processing of emotionally laden information; (4) to obtain EEG measures of hemispheric asymmetry at rest and in cognitive (verbal and spatial) and affective (euphoric or dysphoric) tasks.